We propose to extend our studies on the mechanisms by which vinca alkaloids induce remissions in autoimmune thrombocytopenia. We believe that vinca alkaloids are concentrated in platelets, the subsequent consumption of which by macrophages effects direct delivery of these agents in such toxic quantities that further platelet destruction by these phagocytic cells is impaired. We wish to investigate further the use of the platelet as a vehicle for these drugs by means of drug binding, structural alteration, and survival studies, and to examine the effects of ingestion of vinblastine-loaded platelets upon the macrophage (monocyte) cell structure and function. To do this we have developed an in vitro model of ITP. Cell structural consequences of phagocytosis of vinblastine-loaded platelets will be examined by electron microscopy. Functional consequences will be evaluated by studies of viability, chemotaxis, phagocytosis, and cell metabolism. We have demonstrated the therapeutic efficacy of the vinblastine platelet complex in refractory ITP. We propose to enhance the therapeutic efficacy and minimize the side effects of vinca alkaloids in the treatment of this disease by further refining this technique. This will be done by extending our studies in patients refractory to conventional therapy; we will examine the effects of drug dosage, duration of infusion, maintenance schedules, and the effects of vincristine complex. Clinical responses, immunologic alterations, and comparative toxicities will be followed in detail. Further, we plan to use this strategy in other disorders of similar pathogenesis to ITP. We have demonstrated the feasibility of this approach in two patients with warm antibody mediated autoimmune hemolytic anemia. Studies will be extended to other patients in this category. We will explore the possible application of this means of interrupting the immune response to transplantation in laboratory animals.